Doses of ³H-acetaminophen (300-750 mg/kg) that cause necrosis in mice were shown to result in large amounts of radiolabeled material covalently bound to mouse liver protein in vivo (2 nmol/mg of protein or approximately one molecule bound per two molecules of protein in microsomes and cytoplasm). Both covalent binding and hepatic necrosis were dose dependent, and the peak level of binding preceded the development of recognizable necrosis by at least one to two hours. Pretreatment of mice with phenobarbital, piperonyl butoxide or cobaltous chloride, which changed the rate of metabolism of ³H-acetaminophen and altered the severity of hepatic necrosis, similarly affected the extent of hepatic binding of radiolabeled metabolite. Furthermore, the degree of binding in individual mice was always directly proportional to the severity of hepatic necrosis regardless of the biologic variation among various animals. Accordingly, we propose that acetaminophen-induced hepatic necrosis may be caused by the covalent binding of a chemically reactive metabolite to vital hepatsic macromolecules.

Background/Objectives: Retinal vascular occlusions are a significant cause of visual impairment in older adults, resulting in ischemic retinal damage and sudden vision loss. This study evaluates the retinal, optic nerve head (ONH), and choroidal capillary networks in chronic and acute-on-chronic hypoxia compared to normal controls using optical coherence tomography angiography (OCT-A). Methods: We evaluated a prospective study including twenty patients in the hypoxic group (mean age 61.2 ± 10.2) in two phases, chronic hypoxia and acute-on-chronic hypoxia, and 21 control subjects (mean age 59 ± 9.4 years). All patients underwent a comprehensive eye examination, OCT, and OCT-A imaging. The data were analyzed using OCT-A analysis software (Zeiss OCT-A software 2.1.0.55513) and Fiji software (1.51a). Vascular density of the retina and ONH, choriocapillaries, and foveal avascular zone (FAZ) size were measured. Results: The superficial peripapillary vascular density was higher for the control group (0.387 ± 0.03) compared to the hypoxic patients with (0.383 ± 0.03) and without O2 supplementation (0.383 ± 0.03; p = 0.018). No retinal angiographic differences were identified between the two study groups. The ganglion cell layer (GCL) was thinner in the hypoxic group. Both hypoxic subgroups demonstrated denser choriocapillaries (mean 13,073 ± 1812 and 12,689 ± 1815, with and without O2 supplementation, respectively) compared to the control group (mean 9749 ± 2881, p < 0.001 for both groups). Hypoxic patients demonstrated increased area size of choriocapillaries (+O2 supplementation—mean 44,347 ± 10,563; −O2 supplementation—mean 46,984 ± 12,822) compared to the control group (mean 30,979 ± 9635; p < 0.01 and p < 0.001, respectively). Conclusions: Chronic and acute-on-chronic hypoxia did not affect the retinal vascular network, most probably due to the strong autoregulation of vascular function of the retina. However, compared to the control group, GCL, ONH vasculature density, and most choriocapillaries indices were significantly altered among hypoxic patients.

Rationale: COPD diagnosis requires relevant symptoms and an FEV1/FVC ratio of <0.7 post-bronchodilator on spirometry. Patients are frequently labeled as COPD based on clinical presentation and admitted to the hospital with this diagnosis even though spirometry is either not available or has never been performed. The aim of this study was to evaluate the accuracy of COPD diagnosis based on post-bronchodilator spirometry, following hospital admission for COPD exacerbation. Methods: This is a retrospective study with a cross-sectional analysis of a subgroup of patients. Demographic and clinical data and pre-admission spirometry were collected from electronic records of patients hospitalized with a primary diagnosis of COPD. Patients without available spirometry were contacted for a pulmonary consultation and spirometry. Three groups were compared: patients with a confirmed COPD diagnosis (FEV1/FVC < 0.7), without COPD (FEV1/FVC > 0.7), and those who have never performed spirometry. Results: A total of 1138 patients with a recorded diagnosis of COPD were identified of which 233 patients were included in the analysis. Only 44.6% of patients had confirmed COPD according to GOLD criteria. In total, 32.6% of the patients had never undergone spirometry but were treated as COPD, and 22.7% had performed spirometry without evidence of COPD. Recurrent admission due to COPD was a strong predictor of a confirmed COPD diagnosis. Conclusions: Among the patients admitted to the hospital with a COPD diagnosis, a high proportion were not confirmed by the current GOLD report or had never performed spirometry. Stricter implementation of the diagnostic criteria of COPD in admitted patients is necessary to improve diagnosis and the treatment outcomes in these patients.